Figure 4. The CDRH3 length distribution of the Kymouse is intermediate between humans and C56BL/6 mice primarily due to reduced VD and DJ insertion rates.

The CDRH3 length distribution of the Kymouse (average 14.3aa) is intermediate between equivalent C57BL/6 repertoires (12.4aa) and human repertoires (16.6aa) (A). For each of five possible contributing factors, we used bootstrapping to estimate the contribution of the factor to difference in CDRH3 length, measured in nucleotides. Where this factor is positively contribution (i.e. is above zero), the factor is leading to differentially longer CDRH3s in the Kymouse; where negative, it leads to differentially shorter CDRH3s in the Kymouse. These statistics reveal that the major factor leading to a reduction in CDRH3 length in the Kymouse, despite access to the same germline repertoire, is the relative lack of VD and DJ insertions (B) (Figure 4—figure supplement 2).

Figure 4—figure supplement 1. The distribution of average CDRH3 length per repertoire is shown for each of the bulk VH repertoires.

The solid lines indicated the population-wide average as calculated and shown in Figure 4 in the main text.

Figure 4—figure supplement 2. VD and DJ insertion length distributions in the Kymouse (grey) versus human (blue) repertoires.

We considered only sequences where a satisfactory IGHD germline alignment was achieved.